SERIOUS ADVERSE DRUG EVENTS JN PATIENTS PRESENTING TO EMERGENCY DEPARTMENTS

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SERIOUS ADVERSE DRUG EVENTS JN PATIENTS PRESENTING TO EMERGENCY DEPARTMENTS

AND ADMITTED TO HOSPITALS IN NEWFOUNDLAND AND LABRADOR

by

©Khokan Chandra Sikdnr, BSc (Hons), MSc, MAS

A thesis submitted to the School of Graduate Studies in part in I fulfillment of the requirements for the degree of

I>OCTOR OF I'HILOSOI'HY in

Community Health

Division of Community Health, Faculty of Medicine MEMORIAL UNIVERSITY OF NEWFOUNDLAND

April2011

St. John's, NL Canada

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Abstract

The primary objective of this research was to examine the e:-.:tent of adverse drug events (A DEs) in three age-related subgrmzps ofpaticms (children aged 517 years. adults

aged 2:18 years and elderly aged :;::65 years) either presenting to emergency departments (EDs) or admitted to hospitals in the Canadian province of Newfoundland and Labrador (NL). As secondary objectives. this research classified A DEs according to severity and preventability (wherever possible) and identified patients' demographic and clinical characteristics that can predict occurrence of A DEs.

This dissertation research was comprised of three empirical studies. each of which led to a manuscript for publication. The first and second studies used retrospective reviews of patients· ED charts to determine prevalence. severity. and preventability of

A DEs among children and adults presenting to EDs. The third study used a population- based retrospective coho11 design over a 12-year period to detect adverse drug reactions (A DRs) using diagnosis codes in the hospital discharge abstract. The aim of this study was ^todetermine the incidence of A DRs among elderly hospitalized patients and to assess patient-related risk of A DRs.

We found that 2.1% (95% Cl: 1.6-2.6) of pediatric ED visits and 2.4% (95% Cl:

1.8-3.0) of adult ED visits were due to serious A DEs. of which 20% and 29%.

respectively. were considered preventable. In the cohort of elderly hospitalized patients.

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the incidence of ADRs was 15.2 per 1.000 person·years {95% CJ: 14.8-15.7). Children with and without ADE·rcla!Cd ED visits were similar with respect to mean age and mean number of medications. whereas adults with ADE·related ED visits were older.

prescribed more medications and had a higher number of comorbidities compared to their non-A DE counterparts. In elderly hospitalized patients. comorbidity from chronic diseases and the severity ofpaticnr"s underlying illness. rather than advancing age and sex. increased the likelihood of recurrent events. The drug classes.associated with or implicated to A DEs were dissimilar among the three age-related subgroups of patients.

I3y comprising the findings of the three studies together. we concluded that an ADE prevention strategy should be targeted at patient-specific physiologic and functional characteristics, and high-risk medications. as opposed to focusing individual's chronological age.

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Dedication

To my parents Gaur Hari and Pushpa Rani Sikdar:

Your son finally finished school

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Acknowledgement

I am eternally grateful for the loving support and enduring patience from my wife-Madhabi and our son-Dipto. Madhabi has not only been a tireless supporter of my academic pursuits. but also she shares the joy of parenting our son Oipto. who came along the midst of my doctoral journey.

I would like to express my whole hearted gratitude to Dr. Vccrcsh Gadag.

supervisor of my dissertation. for his advice and wisdom given with positive synergy and attitude. I lc made every effort to make my work significant and worthwhile. I would like

to thank members of my supervisory committee. Drs. Brendan Barrett and Peter Wang.

whose feedback with respect to the technical and editorial aspects grounded my thesis in reality. I also wish to thank Dr. Michael Murray. the fanner Associate Dean of the Division of Community Health. who originally suggested me to go on for a doctoral program.

I must ackno\.vlcdgc the support of the Newfoundland and Labrador Centre for Health Information (NLCHIJ. without which my access to the data used for this dissertation would not be possible. A special thank you to my colleagues and friends in the Research and Evaluation Department at NLCHJ for their assistance and

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encouragement along the way. I am specitically indebted to Reza Alaghehbandan, Kayla Col! ins and Don MacDonald. who have been trusted mentors and friends with due encouragement during my doctoral sttLdy: JetT Dowden and Nicole Edwards, who helped me through editing the first and tifth chapters of my thesis: and Jennifer Donnan.

Juliaru1~ Melendy. and Lillian Wilson. \\hO provided their cordial assistance in drug

categorizations as wei! as identification of appropriate diagnosis codes for adverse drug reactions and comorbidities.

Thanks also extended to the Canada Health lnfoway and Health Canada, for assisting \\ith the funding support for the tirst t\\0 of the three studies comprising this dissertation.

Finally. a special thank you to the co-authors on the two papers published in the journals of Pharmacoepidemiology and Drug Safety and Annals of Pharmacotherapy.

and those on the third paper submitted for publication in a peer.reviewed journal.

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List of Tables

Table 2.1: Demographic and clinical characteristics of patients selected for chart review (11 = 158) , ... 56

Table 2.2: Distribution ofADEs/PADEs by severity and preventability categories ... 57 Table 2.3: Comparison of factors associated v-.ith drug-related and not drug-related visits

to ED .. ... 58

Table 2. 4: Medication class associated with drug-related and not drug-related visits to ... , ... 59

Table 3.1: Demographic and clinical characteristics of 334 patients selected for chart

re~w _ _ _ _ _ _ .. _ .. _ . . . . _ ..

_e

Table 3.2: Prevalence of ADEs!PADEs by age and gender .... . ... 88 Table 3.3: Factors associated with drug-related visits (ADEs!PADEs) to EDs .. . ... 89 Table 3.4: Number and rates of preventability of adverse drug events by severity ... 91 Table 3.5: Number and rates of clinical complications associated with ADEs/PADEs ... 92 Table 3.6: Distribution of medication class implicated in the 55 ADEs/PADEs patients.94 Table ~.1: Charlson comorbidity conditions (with weights) present at baseline in

hospitalized patients aged 65 years and older. Ne" tOundland and Labrador.

1995/96 -2006/07.. .. ... 120 Table 4.2: Drug categories responsible tOr adverse drug reactions (A DRs) in hospitalized

patients aged 65 years and older. Newfoundland and Labrador, 1995/96 - 2006/07 ... 124

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Table 4.3: Top 30 drug groups most commonly implicated in adverse drug reactions (ADRs) in hospitalized patients aged 65 years and older. Newfoundland and Labrador. 1995/96 -2006/07 .. ... 127 Table 4.4: Descriptive data on ADR incidence by age. sex. comorbidity and severity of

illness .. ... 132

Table 4.5: Zero-intlated negative binomial regression predicting the occurrence and number of A DRs according to the selected patient-related factors ... 139 Table 4.6: Zero-intlated negative binomial regression predicting the occurrence and

number of A DRs according to the Charlson comorbidities .. .. ... 142

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List of F igures

Figure I.\: Relationship between A DEs. A DRs. Potenlial ADEs and MEs ... \\

Figure 2.1: Illustrative flow·chart for identification of pediatric patients with A DEs .... AS Figure 3.1: Illustrative flow-chart for identificalion of A DEs in adult patients presenting

to EDs ... .. ... 77

Figure 4.1. Illustrative tlowchart for data linkage system to identify A DRs in the elderly

hospitalized patients .. .. ... \\\

Figure 4.2. Predicted probabilities of intercept-only Poisson. NB. ZIP and ZrNB models compared with the observed probabilities of ADR counts ... 136

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ADE ADR AE AIDS

BDBC CCI CI CIHI CPS!

DAD DRP ED EHR ENT HSC lCD ICD-10 ICD-10-CA

ICD-9

List of Abbrevia tions

Adverse Drug Event Adverse Drug Reaction Adverse Event

Acquired Imnwnodeficiency Syndrome Benefit Driven Business Case Charlson Comorbidity lnde:\

Confidence Interval

Canadian Institute for Health InfOnnation Canadian Patient Safety Institute Discharge Abstract Database Drug·relmed Problem Emergency Depanment

Electronic Health Record Ear. Nose. Throat Health Science Centre

lntemational Classiticmion of Diseases International C\assitication of Diseases 101h Revision

International Classification of Diseases I 01h Revision - Canadian Enhancement

International Classification of Diseases 91h Revision

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ICD-9-CM

IOM LRT

ME NB NL NLCHI NSAID OR PADE P-Y

RFT RR

SAS SCMH SD SES SPSS

us

USA ZINB

International Classification of Diseases 9¹¹¹Revision Clinical Modification

Institute of Medicine Likelihood Ratio Test

Medication Error Negative Binomial Newfoundland and Labrador

Newfoundland and Labrador Centre for Health lnfonnation Non-:steroidal anti-inllammator) drug

Odds Ratio

Possible Adverse Drug E\ ent Person-Year

Request for Proposal Rate Ratio

Statistical Analysis Software St. Clare's Mercy Hospital Standard Deviation Socioeconomic Status

Statistical Package fOr the Social Sciences United States

United States of America Zero-Jntlated Negative Binomial

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ZIP Zero-intlated Poisson

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List of Appendices

APPENDIX A Ethics approval from the Human Investigation Committee of

Memorial University of Newfoundland ... . . ... 188 APPENDIX 8 Permissions to lndude Copyright Mllteriuls ... 191 Appe-ndix 8.1 Copyright Permission by the Pharmacoepidemiology and Drug Safety Journal ... 192

Appendix 8.2 Copyright Permission by the Annal.\ (?f Pharmacotherapy .loumal .198 Appendix 8.3 Copyright Pennissions to Include Figure 1.1 in the Thesis ... 101 APPENDIX C Trigger Assessment Tool and Data Collection Tool Used to Review of ED Charts for Detecting A DEs in Jlcdiatric Paticnts ... 204

Appendix C. I. Pediatric ADE Trigger Assessment Tool.. ... 205 Appendix C.2. Pediatric ADE Dnta Collection form.. .. ... 208 APPENDIX D Trigger Assessment Tool;md Data Collection Tool Used to Review of ED Charts for Detecting A DEs in Adult Patients ... 219

Appendix D.\. Adult ADE Trigger Assessment Tool ... 220 Appendix 0.2. Adult ADE Data Collection Form .. .. ... 222 APPENDIX E Estimation of ADE/PADE Prevalence in Adults Presenting to EDs:

Sample Weight Adjustment to Account for the Sampling Fraction ilnd Strutificiltion in the Sampling Design ... 23-1 APPENDIX F Multi(lle Regression Models for Analysis of ADR Count Oata ... 249 APPENDIX C Curricuhnn Vitac ... 266

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List of Publications

The following publications have been derived from the work of this dissertation.

Papers

Sikdar KC. Alaghehbandan R. MacDonald D. Barrett B. Collins KD. Gadag V. Adverse dmg events among children presenting to a hospital emergency dcpartmcnl in Newfoundland and Labrador. Canada. Pharmacoepidemiof and drug sq( 19: 132-140.

2010.

Sikdar KC, Alaghehbandan R. MacDonald D. Barrett B. Collins KO. Donnan J. Gadag

V. Adverse drug events in adult patients leading to emergency department visits in Newfoundland and Labrador. Canada. Ann Pharmacotlter_201 0; 44:641-9.

Sikdar KC. Dowden J. Alaghehbm1dan R. MacDonald D. Wang PP. Gadag V. Adverse dn1g reactions in elderly hospitalized patients: a populmion-based retrospective cohon study. NL. Canada. (Submilledfor publication in the Journal of Clinical Epidemiolo&rv).

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Abstract presented and published

Sikdu KC. DO\vden J. Alaghehbandan R. MacDonald D. Gadag V. Modeling count data with an application to adverse drug reaction in hospitalized patients. In: Proceedings of the 2009 Annual Meeting of Statistical Society of Canada: May 31 -Jun 3. 2009:

Vancouver. BC. Canada.

Sikdar KC. Alaghehbandan R. Donnan l MacDonald D. Gadag V, Barrett B.

Emergency Department visits in adult patients caused by Adverse Drug Events.

Newfoundland and Labrador. In: Proceedings of the 2008 Data Users Conference- Linking the Health Information Chain: Sep 21-23.2008: Otta\\a. ON. Canada.

Dmman .1. Sikdar KC. Alaghehbandan R. MacDonald D. Gadag V. Barrett B. Validation of an Adverse Drug [vent Trigger Assessment Tool. In: Proceedings of the 2008 Annual

General Meeting oft he Canadian Society of Hospital Phannacists ·Ride the Tide: Aug 9- 12. 2008: Saint John. NB, Canada.

Sikd:tr KC. MacDonald D. Alaghehbandan R. Barrett B. Collins KD. Adverse drug

events among adults in emergency depm1ments. NewfOundland and Labrador. Canada: a preliminary analysis. In: Proceedings of the 23rd International Conference on Pharmacoepidemiolog) and Therapeutic Risk Management: Aug 19-22. 2007: Quebec City. QC. Canada: Phormacoepidemiofogy ond Drug Sc!fe~l' ]007: 16 (Suppl 2):SJ88.

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Sikdar KC. MacDonald D. Alaghehbandan R. Barrett B. Gadag V. Emergency department visits caused by adverse drug events. Nev.i'oundland and Labrador. Canada.

Presentation to the Community Health Seminar Series: Nov 21. 2008; Faculty of M~dicine. Memorial University of Newfoundland. St. Jolm"s. NL. Canada.

Sikdar KC. MacDonald D. Alaghehbandan R. Barrett B. Gadag V. Adverse drug events in children and adults leading to emergency depm1me111 visits in Newfoundland and Labrador. Presemation to the Patient Safety Research Affinity Group Meeting: Sep 16.

2009: Newfoundland and Labrador Centre for Applied Health Research. St. John's. NL Canada.

The following abstract has been submitted for presentation.

Sikdar KC. Donnan .1. MacDonald D. ADE Monitoring in Newfoundland and Labrador:

Opportunities for Provincial Dmg Information Systems. Submitted for oral prcscmation to the e·Health 2011 conference: May 29 Jun 1. 2011: Toronto. ON. Canada.

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Research Reports

NewfOundland and Labrador Centre tOr Health ln!Onnation. Serious adverse drug events in adult patients leading to emergency department visits: a baseline study to investigate bene tits of a provincial phannacy network. Pre-pharmacy report I of 4. Report submitted to Health Canada and Canada Health Infoway. Government of Canada: 2009.

NewtOundland and Labrador Centre tOr Health ln!Onnation. Serious ad\'erse drug events in pediatric patients leading to emergency depat1ment \ isits: a baseline study to i1westigate benefits of a provincial pham1acy network. Pre-phannacy report 2 of 4.

Report submitted to Canada Health lntOway. Govenm1ent of Canada: 2009.

Additional publications in peer-reviewed joumals and presentation to national and international conferences during my doctoral studies are given in my curriculum vitae in Appendix G. Gi,en that they \\ere originated either from lll) \\Ork related to one of the doctoral courses or other collaborations. but not from the thesis, they have not been inclllded in the thesis.

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Personal Contribution to the Program of Research

This dissertation includes five chapters in total. with chapter I for a general introduction and overview, then chapter 2. 3 and 4 for reporting three empirical studies (each of which led to a manuscript for publication) and the final chapter for linking all three studies thematically together with providing implications and recommendations from the disset1ation.

During my doctoral studies. I worked in the Research and Evaluation Department ofl\e\\ tOundland and Labrador Centre tOr Health Information (NLCHI) as a statistical consultant until April 2007. and since then have been working as a senior biostatistician in addition to my role as a co·applicant on the investigation team for the tirstl\\0 studies.

The work in chapter 2 and 3 is based on my work as a co-investigator on the larger benetit evaluation of the provincial drug infonnation system (also refers to as the Newfoundland and Labrador Pharmacy Network). The two studies leading to these two chapters were made possible through funding by Canada Health lnfoway and Health Canada. as well as through in-kind contributions by NLCHJ.

My motivation for conducting this doctoral research \vas based on my experience on reviewing the literature to identify reliable and valid instruments measuring serious

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adverse drug events among the people living in the community setting and subsequently presented to emergency departments. In both studies I was responsible for study conception. design and data management. In the design stage. I was the lead for preparing the trigger assessment tools and datcl collection tools used for collection of study data through patients' chU11 review. selecting study sample. and communicating to the research team with issues arising from data collection process. Following data entry perforn1ed by NLCHI employees. I perfonned data processing. including collation of data from multiple data entry points into one file. establishing measures for data validation checks. tlagging records with inconsistent entries. and taking appropriate measures to mitigate issues.

Unlike the tirst two studies. the third study leading to chapter 4 was not pm1 of benefit evaluation of the provincial drug information system. The study was added into the disse11ation by enabling the use of administrative health data to capture and document a wide range of serious adverse dn1g reactions in hospitalized pntients. l designed this study and wrote the SAS programs for data extraction and derivation of necessary variables for the study. The study data were derived through a data linkage system that linked tive administrative health databases: I) discharge abstract database. 2) health insurance registry database. 3) mortality system. 4) neighborhood socioeconomic status database. and 5) postal code conversion database.

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In each of the three studies. I conducted all the anal) sis. except some assistance requiring clinical knowledge (e.g .. categorizing patients· health conditions and dmg Lttilizations) obtained from medical research and pham1acy research specialists. I performed interpretation of data. and drafted manuscripts for publication. l have presented the results in several international and national conferences. !took pm1 in a series of presentations to academia. and provincial special interest groups. resulting in a '' idespread and ongoing dissemination of findings throughout the course of this doctoral research. I CO·authored a final report for each of the tirst two studies that were submitted to Canada Health Jnt(may and Health Canada. The two manuscripts that were written based on the findings of the first two studies have been published in the February 2010 issue oft he JOLJrnat of Plwrmacoepidemilo~~Y and Drug S(!fery and the April 2010 issue of The Annals of Pharmacotherapy. The other manuscript based on the findings of the third study has been submitted for publication in the Joum(ll <?(Clinical Epidemiology. A Jist of publications and abstract presentations from my doctoral research is given at page .X\iii-.x.xi).

For all work reported in my dissertation. I made major intellectual and practical contribution in each of the general research stages specified in the guidelines for thesis and repot1S by the Memorial University"s School of Graduate Studies: i) design and identification of the research proposal. ii) practical aspects of the research. iii) data analysis. and iv) manuscript preparation. This enabled me to be the principal aLnhor in all the three manuscripts and in most of the conference and meeting presentations. The

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research t~am members who substantially contributed to meet the criteria for authorship stated in the Unifom1 Requirements for Manuscripts Submitted to Biomedical Journals

have been listed as co·authors.

Collectively. the three studies and three papers constitute a thesis that forms the basis for an ongoing and future program of research in the area of adverse drug events (/\DEs). and our findings add to the existing literature by focusing on serious ADEs leading to health service utilization and draw attention to the need for prevention efforts that target patient in Canada at high risk for /\DEs. and ultimately add to the discourse to improve patient safety.

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CHAPTER 1 Introduction and Overview

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1.1

The context of Patient Safety: Driving Forces and Policy Implementation

Patient safety is a major issue for everyone- healthcare professionals. providers and patients. The potential for medical care to cause hann has long been recognized throughout the history of medicine. However. the awareness of the problem of patient safety \\as stimulated follO\\ing the rising rate of litigation in the 1970s and 1980s. which led to the development of risk·management programs in the United States. and later elsewhere ¹• Starting from almost exclusively a legal and financial focus to protect institutional concerns. the error prevention movement has accelerated through addressing clinical issues and acting as a gateway to the underlying problem of patient safety.

The topic of patient safety has become a focus of clinical care and research in recent years. Several studies have revealed the scale of harm to patients from healthcare management rather than disease. In the United States. the Harvard Medical Practice Study~ reported that patients were unintemionally harmed by treatment in almost 4% of admissions in New York State. The resulting disability was slight or temporary for 70%

of these patients. but in 7% it was pennanent and I-I.% of these patients died. panly as a result of their treatment. In the United Kingdom. a review of patient records indicated a

\0.8% adverse event rate. of which about half were judged to be preventable ³. The Bristol inquiry was one of the few high-profile cases in Britain that painted a picture of a flawed system of care with poor teamwork between professionals by providing inadequacies at every point. from referral to diagnosis. surgery. and intensive care. The inquiry has continued to focus professional and public al\e!llion on patient safety in a manner unprecedented in both its depth and for the extent of professional involvement"·

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Patient safety practices include scientitic knowledge thai continually informs improvement of efforts and reduces risk of adverse events related to exposure to medical care 0 . The increasing incidence of adverse events in health care has led to a gro\\ ing concern in a number of countries about patient safety. and thus this issue remains a fundamental principle of patient care and a critical component of quality management 1•

Among the recent works on patient safety. the Institute of Medicine's (!OM) landmark report "To err is human: building a M!fer healrh -\YS!em". a publication based·on a systematic review of patient safety·related medical literature. has aroused an enonnous

response 7. Having fOcused on the potential tOr hann in modern medicine. the !OM repon investigated preventable adverse drug events. the role of systems failures in the aetiology of medical errors. and the effects oft he healthcare workforce on safety 2· 8· 9. The repo11 estimated that 44.000 to 98.000 patients die every year because of medical error in the Unitt'd States alont'. Medical errors included all problems that commonly occur during the course of providing health care such as adverse drug events and improper transfusions. surgical injuries and wrong-site surgery. suicides. and mistaken patient identities. Because reducing medical errors can save human lives and health care costs.

the IOM repo11 called for a broad national ef!011 to include establishment of a Centre tOr Patient Safety. expanded reporting of adverse events. development of safety programs in health care organizations. and attention by regulators. health care purchasers, and professional societies ⁷. A number of legislative and regulatory initiatives to document medical errors and to search tOr solutions have been staned based on the strong

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recommendation of the report to set a goal of reducing error related mo11ality in the United States by 50% over a 5-year period 6.

Several important new initiatives in the last few decades have been undertaken.

especially by developed nations to build and advance safer health care systems for their populations. These initiatives underline the increasing attention paid to patient safety.

The U.S. government established the National Patient Safety Foundation aimed at making health care safer for patients through an unprecedented partnership of health care practitioners. institutional providers. health product providers. health product manufacturers. researchers. legal advisors. patient/consumer advocates. regulators. and policy makers 10. The Australian Patient Safety Foundation pioneered a sophisticated approach to patient safety by providing leadership in the reduction of harm to patients in all hcalthcarc environments since 1988 ¹¹· ¹~. The National Patient Safety Agency in England contributes to improving the safety of patient care by informing. supporting and influencing organi7ations and people working in the h~alth sector 10. Following numerous legal cases and media stories that highlighted the consequence of unintentional adverse events. patient safety is receiving growing attention in Canada as well 14 . The Winnipeg inquiry in Canada was a notably high-profile case that played a part in raising public awareness and driving policy changes 11 ln 2002, the Canadian government budgeted

$50 million over 5 years for the creation of the Canadian Patient Safety lnstilllte (CPS[) that operated collaborativcly with many health care organintions and regulatory bodies

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to improve patient safety ¹4. The mandate of the CPS! is to provide a leadership role with respect to patient safety issues in the context of improving health care quality. CPS!

facilitates collaboration between governments and stakt·holders to enhance patient satety initiatives to share best practices. and recognize the role of research, knmvledge transfer and evaluation to ensure patient safety 15•

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1.2 Overview of Drug-related Problems

Drug·related problems (DRPs) are a critical component ofpmient safety since these arc the events or circumstances involving drug therapy that actually or potentially interferes with desired health outcomes. Drugs are prescribed for patients to achieve an optimal therapeutic outcome in treating various medical conditions. Despite the fact that

the therapeutic benefits of medications have resulted in hundreds of millions of people living healthier and longer lives everyday. medications arc not risk·frcc. As the number and strength of available drugs increase over time. prescription and utilization of drugs

become more complex. leading to a variety of DRPs H'>. A DRP occurs when a patient experiences. or is lihely to experience. either a disease or symptom having an actual or suspected relationship with drug therapy- meaning that an optimal therapeutic outcome

could not be achieved ¹⁷• In the existing literature ¹^{7' 18}• eight different categories of DR.Ps have been described: untreated indication. improper drug selection. subtherapeutic dosage. failure to receive drugs (includes patient noncompliance). overdosage. adverse drug reaction. drug interaction. and drug used \\it bout an indication. Although many DRPs can be resolved without a major impact on patient health. some of these are a signiticant cause of hospitalization. emergency department visits and subsequent resource

utilization. A US study reported that morbidity and mortality associated with drug-related problems accounted tOr $76.6 billion in health care costs. 17 million emergency department visits. and 8.7 million hospital admissions every year ¹⁹Bates and colleagues

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reported that 76.000 deaths were due to adverse drug reactions mmually in the United States ²⁰. Using the I: 10 ratio of the population of Canada to that of the US. it has been reported that adverse drug reaction fatalities would be ranked as the th leading cause of death in Canada. alter cancer. heart disease. stroke. pulmonary disease and accidents ²¹

An adverse event (AE) is an injury resulting from medical management rather than the underlying disease ²¹A great deal of research has been carried out in an a11empt to identify rates of serious AEs in USA and Australia ²0· 2-'"26• llowcvcr. much less information is available about these events in the Canadian population. This has been acknowledged in the National Steering Committee on Patient Safety report ... Buildin:< a Safer Health Sysrem-A National Integrated Slmtegyfor Improving Patient Sc{(ery in Canadian Health Care"" 21. This report highlighted that Canada is signiticantly behind the United States. the United Kingdom and Australia in accepting that patients are at signiticam risk. in \\atlling to leam about the relevant issue of patient safety. and in investing in the creation of a culture of safety. One of a series of recommendations provided by the Steering Committee was to improve measurement and evaluation processes and adopt designated areas of research. A study by Baker et al. IJ provided the tirst national estimate of the incidence of adverse events among Canadian adult patients.

The estimated rate of adverse events was found to be 7.5 per 100 hospital admissions and. after extrapolation. the number of hospital admissions attributed to adverse events was estimated between 141,250 and 232.250. As noted by the authors. the study provided

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a stm1ing point tOr understanding the incidence of adverse events and the burden of injury resulting from adverse events in Canadian acute care hospitals. Referring to the lack of Canadian data on adverse events. the study strongly recommended fu11her research to explore the types of these events and their contributing factors. Medications are the most frequent cause of adverse events. and SLICh injuries are referred as adverse drug events (ADEs) ~. ~S·ltl. Given that there has been a signiticant investment in the creation of a culture of patient safety in the Canadian Health System tOIIo\\ ing the recommendation of the National Steering Comminee on Patient Safety. it is important to carry out further research to quantify the magnitude of A DEs in the Canadian context. and examine whether there is any association between ADEs and patienHelated factors. Identification of drug·related problems. in particular. those causing hann to patients (e.g .. adverse drug events) and associated risk factors would allow providers to identify early symptoms of A DEs. and to respond to the patients quickly ³¹

1.3 Adverse Drug Events

1.3.1 Adverse Drug Event Terminology

An adverse event is defined as '·any untO\\ard medical occurrence that may present during treatment with a pharmnceutical product but which does not necessarily June a causal relationship with this treatment" lJ In other \\Ords. an AE may cause hann

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in a patient administered a drug but the event may not necessarily be caused by the drug.

When an adverse event refers to ··circumstances that involve a patient's drug treatment that actual!)'. or potentially. interfere with the achievement of an optimal outcome". this problem is termed as a drug.related problem I ':I n_ Drug-related problems include all issues that can potentially am:-ct the success ofphannacotherapy in a given patient. These issues are described by several commonly used tem1s to denote a non·beneficial effect from a drug: adverse drug events. adverse drug reactions. medication errors. drug toxicities and side effects. etc.

The term "adverse drug event" (ADE) is delined as any undesirable etlt:-ct caused by the interaction of a drug (prescription or nonprescription) with a patient 1R Events may be the result of nomwl or inappropriate use of a medication. and could range from minor reactions such as a skin rash to serious and life·threatening events. and even death. A DEs can arise from inappropriate prescribing of a medication (e.g .. misdiagnosis.

inappropriate medication. inappropriate dose. inappropriate regimen. etc.). medication errors. self-medication. side effects. allergies. genetic predispositions. drug·drug interaction. drug·disease interaction. or patient non-compliance (taking more or less of a drug than the prescribed amount).

Adverse drug reaction (/\DR) is a tenn used to describe the undesirable effects of medications. According to the World llca!th Organization, an ADR is "Any response to

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a drug ''hich is noxious and unintended. and which occurs at doses nomwlly LlSed in humans for prophylaxis. diagnosis. or therapy of disease. or for the modification of physiological function" ³⁴Clearly. this definition of ADR requires a judgment as to noxiousness of the response as well as to the intention of an unspecified party. Kramer ( 1981) ¹' argued that whether an e\ent is ad\erse or no'<ious depends on the clinil..:a1 setting and the intentions of the treating physician. and that his or her judgment should be made separately for each case.

The term ··Medication errors·· (ME) include mishaps that occur during prescribing. transcribing. dispensing. administering. adherence. or monitoring a drug.

Examples of medication errors include misreading or miswriting a prescription.

Medication errors thai are stopped before hann can occur are sometimes called ··near misses"". ··close calls"" or more fonnally. a potential adverse drug event (Figure 1.1 ). Not all prescribing enors lead to adverse outcomes. Medication enors are more common than adverse drug events. but result in harmful events less than I% of the time; about 25% of adverse drug events are due to medication errors 12. Figure 1.1 adapted with permission (Appendix B.3) from Morimoto et. a1. ~⁸and Nebc:ker et al. ³~ demonstrates the relationship among medication errors. A DRs. A DEs and potential A DEs.

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Potential Adverse Drug E\'ents

Adverse Drug Events

(all gray areas)

Figure 1.1: Relationship between A DEs, ADRs, Potential Adverse Drug Events, and MEs

Although A DEs and A DRs arc sometimes used interchangeably. they do not have the same meaning. An /\OR refers to adverse effects of medications when they are used appropriately at normal doses, either for prophylaxis. diagnosis or trcauncnt .lb. The term

ADE includes A DRs in which no error occurred and/or complications that result from medication errors. The term ADR implies that drugs arc properly prescribed and

administered. and thus the reactions are difficult to prevent. their reduction mostly depends on development of new and safer agents. HO\\Cver. A DEs due to medication errors are preventable and developing strategies to prevent these reactions me relatively easy ³⁷. The tenn ADE has been broadened by Nebeker et al. 12. in which it refers to as

··any undesirable effect related to the use or misuse of a drug (prescription or

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nonprescription)"'. and is considered to be a relatively better definition given that it includes errors of omission. An error of omission involving the failure to provide an effective treatment in the setting of a severe disease poses \ery substantial risks for patient safety and outcome.

A ··possible adverse dmg event" (PADE) is defined as an event that may have been related to a cmTent medication: however. it may also have been due to another cause (e.g., viral infection), and therefore. confim1ation of ADE is not possible. When ADE studies were carried out based on retrospective study design. in particular reviewing patients' medical charts. the term of possible ADE was found favorable over potential ADE due to the fact that necessary information may not have been available in patient charts to identify a confirmed reason leading to adverse event.

Dutchman Mcyler was the first who provided a systematic overview of ·side effect of drugs. in \951 JU~,~_ The term "side effect·· does not imply that the response is adverse. A side effect usually includes any response other than the main therapeutic effect of the drug and may be desirable. undesirable. or inconsequential .13 An event of side effect rnight also irnply that the effect can be beneficial. These events can range from hannless epiphenomena to innocuous m1isances to harmthl and possibly irreversible injuries to death. Both tenns ··side effect" and ··A oR·· imply that the observed effect is caused by a particular drug. Because A DRs are often erroneously classified as ··side

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effects··, it has been reconunended the term ··side etlfcts·· no longer be LlSed as this tends to minimize the injury from drugs P 40.

1.3.2 Severity and Preventability of Adverse Drug Events

The severity of A DEs is usually detennined \\hen detection of A DEs involve prospective follow-up of sllldy patients or manual review of medical charts. Previous studies ~⁰~¹-⁴¹have classified A DEs into tOur categories: I) lfltal. 2) life threatening. 3) serious and 4) significant. An ADE was considered to be significant if the event caused

symptoms that while harmful to the patient pose little or no threat to the patient's life function. An event is referred as a serious ADE if it caused symptoms associated with a serious level of risk while it was not high enough to be lite threatening. An ADE is also serious if it caused persistent alteration of life function. An ADE is considered to be life threatening \\hen an event caused symptoms that if not treated. \\Ould put the patient at risk of death. An ADE is fatal when the event results in death of a patient ~¹• Classilication of the severity of A DEs usually takes into consideration several pieces of infonnation such as the impairment of the patient's quality of life: hospitalization or prolonged hospital stay: temporary or pennanent malfunction of an organ system:

temporary or pennanent inability to work: elevated or depressed lab values resulting in medical interventions: life threatening: and discontinuation or substitution of the drug 44 .

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Gun\ itz eta\. J~ noted examples in darit'ying severity of A DEs. A nonw1icarial skin rash.

a fall without associated fracture. hemorrhage not requiring transfusion or hospitalization.

and oversedation were examples of significant A DEs. Serious A DEs included urticaria. a fall with an associated fracture. hemorrhage requiring transfusion or hospitalization but without hypotension. and delirium. Any harm such as hemorrhage with associated hypotension. hypoglycemic encephalopathy. profound hyponatremia. and acute renal tflihu·e requiring hospitalization \\ere given as examples of life-threatening A DEs.

Preventable A DEs \\ere those due to error that could have been prevented by any means available ⁴⁰Preventability was categorized as definitely preventable. probably preventable. probably not preventable. or delinitely not preventable. When the data

collection involves a physician and/or pharmacist reviewer. the determination of preventability is usually based on the reviewer"s presumed knowledge at the time the drug was prescribed. This infom1ation was used in conducting subjective assessment of categorization following consensus between reviewers "'1• Although the data collection and recording in this thesis follows these categories. results were often collapsed into preventable and non-preventable categories to reduce sampling error associated\\ ith small number of events"'~. A preventable ADE is an adverse event attributable to a medication error. whereas an event causing injury. with no error involved. is known as a non-preventable AD E. An example of a preventable ADE includes allergic reaction in a patient known to be an allergic to a pm1icular drug. On the contrary. allergic reaction in a patient not known to have dmg allergy is an example of a non-pre\'entable ADE ⁴~.

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1.3.3 Detection of Adverse Drug Event

Multiple epidemiological methods exist for the detection of acherse drug events.

Different methods of ADE identification include voluntary reporting. chart review. direct observation. patient interview and electronic Sltrveillance. The methodology used depends on the research questions, study design and scope of the study based on available resources.

In voluntary reporting. healthcare professionals. drug manufacturers and drug consumers are prO\ ided a pre-designed form by '' hich the) can report an) suspected drug-related incidents. In the context of ADE reporting. the tenn ·voluntary' reporting is also refetTed to as 'spontaneous· or ·incident' rep011ing. "hicb means reporting is not compulsory JR. Voluntary reporting depends on the ability of health professionals to recognize errors and their willingness to disclose them in error repot1S "⁰. Although this method remains an attractive source of infonnation for researchers. because the infonnation is generally readily available. the problem of under rep011ing greatly limits its utility for patient safety research. Studies have shown that voluntary reports identify only 5% of A DEs "7'49. Daily chart review and solicited repot1ing have detected tive times as many A DEs as voluntary coding in hospital separation or mortality records ~u . .: 1 Intem1ption in work !low. perception that completing a tOm1 does not result in any improvement. lack ofkno\\'ledge that an ADE has occurred, and fear of exposing oneself

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to litigation have been identified as possible reasons why incident repot1S are underutilized ~⁰

Medical cha11 reviews have been employed in retrospective coho11 studies and case~control studies to detect A DEs. Murff eta\ ~⁰summarized chart review studies citing Se\eral high quality studies. including the California Mt'dical Insurance Feasibility Study

' 1• the Harvard Medical Practice Study ~²• and the Colorado~ Utah Study ⁵³In this method

of ADE detection. patient charts usually undergo a two~phase screening process. Initially a trained reviewer. usually a research nurse at the first phase. examines charts using a set of pre-defined screening criteria. Charts identified with at least one of the screening criteria then undergo physician review in the next phase to judge whether physician revievvers believe an adverse event had occurred based on the infom1ation in the chart.

Usually two physicians independently review each chart flagged at the first phase. and if

the physician reviewers disagree on whether an adverse event occurred. the physicians come to a consensus or involve a third pat1y to resolve the disagreement ⁵⁰

There are several limitations with the use of patient chart review to identify ADEs. First. identifying and classifying ADEs tlu·ough chart review requires implicit judgment by the researchers: this process may introduce bias 54• Second. this method for ADE identification has been predominantly used in retrospective studies. where

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supplemental information cannot be obtained and this may cause underestimation of A DEs ⁵-J 55• Third, there is a tendency of the nurse reviewer at the first phase to flag a large number of charts as a probable ADE even if there may be very linle documentation of having an ADE. A study focusing on reliability and validity of judgment conceming adverse events repo11ed that the positive predictive value of the initial screening process was as !ow as 21%. and as a result physicians reviewed a high number of false positive charts,, A tina!. but possibly the greatest limitation to this methodology. is the overall resources required. '>vhich can be significall! when compared to other screening modalities ~n Since chart re' ie,,s are very costly and time consuming. some investigators have used fewer screening criteria to help reduce the overall resource burden ⁵¹• TheretOre. medical chart review. in general. remains an impractical means tOr routine adverse event detection.

Patient inten iew is another method of ADE detection. A study by Forster eta!. ¹² utilized patient interviews as well as information from sign-out notes. discharge summaries. and laboratory results to prepare case summaries tOr physician reviewers.

A DEs were determined based on review of these case summaries. The study reported that nearly one in five patients experienced an ADE during the transition from the hospital to home. A review paper ⁵⁰citing studies that used patient interview data reported that 10%

to 42% of patients experienced and ''ere aware of an error occurring \\ ith their medical

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care. The major limitation of patient interview is that it requires a substantial reSOllrce commitment.

Computer-based approaches (i.e .. computer-based monitoring programs) have recently been incorporated in research to identify A DEs. This program identifies ·nlcrts'.

which are situations suggesting that an ADE might be present. Following these alerts. a trained reviewer examines patients' hospital records to dctcnninc whether an ADE had occurred ~M. This approach has an advantage over chart review in that it is a more cost- effective method~-~. Computer-based programs have been shown to identify more cvcms than spontaneous reporting~~~. However. there is limited use of this method to identify A DEs because of the huge cost for institutions to develop this system and the uncertainty regarding its effectiveness. Previous studies have used medical chart review and compared the results to computer based programs and other methods to identify A DEs ~s-

5'~. A study by .lha eta\ Sll reported that more events were identified through chart review

compared to the computer-based monitoring strategy and voluntary reporting (13.3 vs.

9.6 vs 0.7 /\DEs per \.000 patient-days. respectively). In a study with nursing home residents. Gur\\'itz et al ~Q ascertained A DEs by utili7ing both chart review and incident reporting by health care providers. It was reported that the method of chart review identified many more A DEs than using health care provider reporting (83% vs. 17%.

respectively).

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While each method illustrated Jbove has its own strengths and limitations. the scope of available resources etten dictates which methodology is used for detecting ADEs. In Newfoundland and Labrador (NL). having a sample frame through an electronically available Emergency Depm1ment (ED) triage database allowed for sekction of a representative sample to carry out two of the studies (described in the next sections) included in this dissertation. The step-wise chart review method that used a

trigger assessment tool and subsequently a data collection tool. illustrated in chapters 2 and 3. greatly simplified the chart review process by allowing relatively rapid and systematic examination of charts to extract relevant data for the detection of A DEs.

Additionally. in NL. there is a unique opportunity to study a large. geographically isolated population using pre-existing daw sources. Utilization of the hospital discharge abstract database for assessing ADRs and its linkability with other administrative data was found to be a cost effective method that offered a potential to capture a large population of patients. This method -.vas also employed in detecting A DRs used for this disse11ation. A brief description is provided in the next sections of this chapter. along with further detail in chapter 4.

1.3.4 Measurement of Adverse Drug Event Occurrences

A central task in adverse drug eve111 epidemiology is to quantify the occurrence of A DEs in study populations. In order to express the extent of the problem resulting from

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ADE occurrence. we need to be able to measure the frequency of ADE occurrences.

Incidence rate. cwnulativc incidence and prevalence arc the three basic measures of .. disease .. or .. incident" occurrence. Although A DEs are tenned as an incident rather than a disease. definitions of tenninologies to measure the frequencies discussed in this section mostly with reference to a disease. This is just to be consistent with the epidemiology and public health literature in defining and illustrating tenninologies.

1-JO\\ever. a concluding paragraph was given with respect to ADE occurrence to claritY the fact that these tenns can be used to express the extent of an incident as well.

The incide11Ce rate is the number of new cases of disease of interest that occur during a specified period of time in a population at risk for developing the disease. In estimating incidence rate. the number ol· ne\v cases of disease is divided by the sum of the time periods of observations for all individuals in the population. Because the denominator of the incidence rate is the sum of the persOJHimc of the at risk population.

it is also known as the incidence density mre or person-time incidence rare OO.bl The cumulatil·e incidence refers to the proportion of people who convert. during a specilied period of time. from non-disease to disease. If risk is defined as the probability of an individual de\'eloping a disease in a specified time interval. then cumulative incidence is a measure of average risk. Cumulative incidence is calculated as the nmnber of new disease cases divided by the number of persons at risk of developing the disease during that period of time. The critical element in the detinition of incidence density or cumulative incidence is new cases of disease. These two terms arc a mcaSllrC of events for which the disease is identified in a person who develops th~ disease and did not have the disease previously.

Prewilence measures the proportion of a population that is affected by disease or incident at a specitied time. Prevalence is calculated as the number of disease cases

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present in the population at a specified time divided by the number of persons in the population at that specific time. As a measure of disease occurrence, prevalence can be viewed as a slice through the population at a point in time at which it is detem1incd who has the disease and who docs not(-~. Prevalence can be used in two ways-point prevalence and period prevalence. The tenn poim prevalence refers to prevalence of the disease measured at a point in time. The other term period prero!ence measures prevalence of the disease at any time during a certain period. such as during a single calendar year. When we think of a survey as the source of obtaining data. it is vi11ually impossible to survey an entire city on a single day. Therefore. prevalence measured from survey data often conceptually think of in terms of single point in time, but in reality. the survey would take much longer. This is why. in some situations researchers arc to choose prevalence that measures how many people have had the disease at any time during a given period. In estimating period prevalence. it is considered that some people may have developed the disease during that period. and others may have had the disease before and died or been cured during that period.

The numerator of prevalence includes a mix of people with different durations of disease or incident, and the denominator includes the number of population at that specified time as opposed to population at risk. Thus. prevalence is not a measure or risk.

If the aim is to measure risk. the term incidence must be used. because in contrast to prevalence. it includes only new cases and a specific time period during which these events occurred I'lL 6~.

Similar to any disease occurrence. the frequency of A DEs can be measured using rates or proportions. Incidence density or cumulative incidence can be treated as rates and are used to comprehend how fast the ADE is occurring in a population. whereas

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pre' alence is a proportion which is used to tell us whm fraction oft he population is affected ⁶¹. When an ADE is an outcome of interest. these events are not inevitable or may not occur during the period of observation. In this situation. prevalence is considered as the measure of ADE frequency. However. in an attempt to measure the frequency of ADE occurrence in a population. it is insutlicient merely to record the number of A DEs occurred in that population. It is also necessary to take into account the length of time contributed by all persons during the period they were in the population ⁶¹^•whichjustities the importance of incidence. Although the tem1inologies discussed in this section have importance to express the magnitude of a disease or incident of interest. which measures to be used to express the frequency of an event depends on the study design that permits identitication of the event through clearly defining when the event occurred. The sources of data from which cases are identified influence how we use measures of occurrence to express the extent of disease or incident.

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1.4 Research Engagement

Over the last decade. the province of Newfoundland and Labrador has undertaken an initiative to develop a province-wide Electronic llcalth Record (EIIR). The EIIR will allow data linkage of major clinical and administrative information systems together to allow authori7cd health care providers secure access to a paticnt"s key health history and care within the heath system. One of the systems under the anns ofEI-IR is the Newfoundland and Labrador Phannacy Network. This system is undergoing a benefit

evaluation using pre and post comparative study designs. The pre-implementation evaluation of the Phannacy Network included several studies aimed at gathering baseline data on drug related problems. including the occurrence of serious A DEs. which has fonned the basis of this dissertation research. This involved two separate studies that used retrospective review of patient ED charts to determine prevalence. severity and preventability of A DEs occurring in children and adults in the community setting and resulting in ED visits. In addition to these studies. a third study. which is not part of the

benefit evaluation of Pharmacy Network. involved the detection and analysis of A DEs among elderly hospitaliLed patients using a population-based retrospective cohort study.

This dissertation research was comprised of these three studies.

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The EHR initiatives in Newfoundland and Labrador included several infOnnation systems. While other information systems (e.g .. Telehealth. Laboratory. Picture Archiving and Communication Systems) considered pa11 of the EHR are out of scope tOr this dissertation. the project ideas illustrating how the Phannacy Network fits in with the overall EIIR implementation plan deserve elaboration.

1.4.1 Electronic Health Record Initiatives in Newfoundland and Labrador

An electronic health record provides health care professionals with online real- time ac(.;ess to their patient's complete medical protilt.". It holds key health information about every person in the province through building a secure and private lifetime record of a person's health and healthcare history. It shares selected aspects of patients' health information. from medications or x-rays to blood tests or vaccines. with all authorized

health care professionals ⁰³Recognizing the impot1ance of the EHR in improving the quality and etliciency of health care. the federal govemment of Canada established Canada Health lntOway (/l!{oway) in 2001 to accelerate the deYe]opment and adoption of Electronic Health Records across the coumry. 11!/0II'ay was provided with $1.2 billion in funding and a 7-year mandate to \\Ork with all jurisdictions in Canada in both planning and implementing their EHR initiatives. With an aim to have 50% of Canadians

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connected to an EHR by the end of2010. hrfoway identified core components of an EHR in their 2003/04 Business Plan M-n_,_

The Newfoundland and Labrador Centre for Health lnfonnation (NLCHI) has received funding from ln}Oway to implement six key building blocks of the 1-::IIR: (I) a unique personal identifier/client registry. (2) a pharmacy network. (3) a laboratory network. (4) tclchcalth. (5) a provider registry and (6) a diagnostic imaging network b5-ot:..

To determine the benefits of the EHR. a number of research initiatives have been lllldertaken to establish baseline data on the delivery of various aspects of health care in r\ewfoundland and Labrador. Once the EHR is in full operation. these studies will be repeated as a means to assess benefits to health care delivery using a pre/post- comparative design.

1.4.2 The Newfoundland and Labrador Pharmacy Network

The Newfoundland and Labrador Pharmacy Network is a provincial drug

infonnation system that will offer province wide online. real-time medication profiles. as well as comprehensive drug infonnation. A personal medication dispensing history built up within the Pharmacy Network involves linking community and hospital pharmacies

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and physician oflices. so that a patient"s historical and cuiTent medication protile is available to health professionals at the point of care. Once all pharmacies in the province are connected to the Pharmacy Network. medication information of a patient will be stored in one record- the patient's profile. It is expected that giving health professionals access to that record will provide many benefits to the patient. as well as the patient's health care providers ⁶³. Health professionals· access to infonnation about the medications a patient takes is expected to improve the quality of the patient\ healthcare.

The information will support better decision making about medications. diagnosis and treatments. and therefore it will be easier and quicker for health professionals to decide whether a patient's new medication will react with others the patient is taking. One of the many expected benefits of the Pham1acy Network in Newfoundland and Labrador is the reduction of serious adverse drug events occurring in the community. With a drug information system and an interactive database alTering accurate real-time prescription

protiles. health professionals would be able to interYene before and after an adverse eYent occurs. This system can help avoid hannful drug interactions and lead to a decrease in the cost of doctor visits. emergency department visits. and hospitalizations 6l 65 The personal medication dispensing history ''ould also result in more appropriate prescribing and dispensing. recognition of contraindication. improved counseling. improved compliance monitoring and reduced abuse of prescription dwgs. A Benetit Driven Business Case (BOBC) submitted by the NLCH! to the Govemment of NL in 1998 suggested the Personal Medication Dispensing History would deliver savings to the health system by reducing ADEs, both in the community and the hospital settings 6.1 The BDBC predicted

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approximately $4.1 million in annual savings to the health system following the implementation of the provincial Phannacy Network.

The provincial EIIR. including the Pharmacy Network. is a collaborative initiative between the Newfoundland and Labrador Centre for Health Information. the Government ofNev.-foundland and Labrador. Canada 1 lealth lnfoway. and the Regional I lealth Authorities. along with many supporting stakeholders. The Provincial Government and

ll~foway have commincd $8.6 million and $17.9 million. respectively in its development

and implementation. The provincial government has committed necessary funding for the ongoing operation of the Phannacy Net\\Ork. In May 2002. NLCHl received approval from the provincial government to carry out a Pharmacy Network project scoping

involving a high level analysis to determine the required functionality of the system. and the resources needed for its implementation. following the completion of the project

scoping and subsequent dialogue and clarification, the government granted approval lOr NLCHJ to move forward with issuing a Request for Proposals (RFP) for the implementation of the Phannacy Nel\\,ork in October 2004. In June 2006. the provincial government and 11!f011"ay signed an agreement to partner on the implementation of the Pharmacy Network. N~wfoundland and Labrador began connecting community pbannacies to the provincial Pharmacy Network in May 2010. Implementation in more than 190 community pharmacies province wide will continue in a phased·in approach

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throughout 20 I 0 and 20 II. After community pharmacies. the next step is connecting health care facilities in the four regional health authorities to the Pharmacy Network 67.

As previously stated. the Newfoundland and Labrador Phannacy Network is undergoing a benefit evaluation using a pre-and post-comparative study design. The pre- implementation evaluation of the Pharmacy Network encompasses several studies to gather baseline data on drug-related problems. Two of the studies were carried out to gather infom1ation on serious A DEs occurring in the community setting and resulting in Emergency Department visits. Given that children and adults have very different drug utilization and in many other ways with regard to medical care. two separate studies were carried out- one in children and the other in the adult population. The overall objectives of these two studies were:

I) To estimate the prevalence of A DEs separately in children and adults presenting

at Emergency Departments in St. John's over a one year period. and to classify these ADEs with respect to severity and prevemability.

2) To use the results of these studies as a baseline; which then will be compared to the results of the repetition of the same studies to be carried out post-Pharmacy Network implementation. Comparisons of pre-post Phannacy Network will be

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made on the overall prevalence of A DEs presenting at EDs. as well as the severity and preventability of the /\DEs,

3) To build research capacity in the province of Newfoundland and Labrador in the area of optimal drug utilization through enhanced infonnation systems.

1.5 Program of Resea rch for Dissertation

The objectives of the two pre-Pharmacy Network studies noted above provided the basis for this doctoral dissertation. While the second and third objectives arc more in line with the larger program of benefit evaluation and achievable following the post- implementation of Phamwcy Network studies. attainment of the first objective was possible based solely on existing data of the two pre-Pham1acy Network studies.

Although. the focus of the benefit evaluation initiatives through these two studies was to determine the frequency of ADEs and their distribution with respect to severity and preventability. investigating how these A DEs differ by patients' demographic and clinical characteristics was one of the primary focuses of this dissertation research. Serious A DEs also have great impact on inpatient admission and length of stay. which is especially more common in elderly patients who usually take multiple drugs to control multiple comorbidities. l-Ienee. considering this high risk group as another subpopu!ation. ADF:s

SERIOUS ADVERSE DRUG EVENTS JN PATIENTS PRESENTING TO EMERGENCY DEPARTMENTS

0Ct.L311

SERIOUS ADVERSE DRUG EVENTS JN PATIENTS PRESENTING TO EMERGENCY DEPARTMENTS

AND ADMITTED TO HOSPITALS IN NEWFOUNDLAND AND LABRADOR

Abstract

Dedication

Acknowledgement

Table of Contents

List of Tables

_e

List of F igures

List of Abbrevia tions

us

List of Appendices

List of Publications

Personal Contribution to the Program of Research

CHAPTER 1

Introduction and Overview

The context of Patient Safety: Driving Forces and Policy Implementation

1.2 Overview of Drug-related Problems

1.3 Adverse Drug Events

Adverse Drug Events

1.4 Research Engagement

1.5 Program of Resea rch for Dissertation